The objectives of the proposed projects are to obtain a better understanding of the nature of lesions and processes leading to cell reproductive death, and to study the interrelationships of factors which influence radiosensitivity, particularly dose-rate and dose-fractionation effects, with an emphasis on their implications for radiotherapy. In recent years much attention has been given to the possible radiotherapeutic advantages of elaborate and expensive treatment modalities involving, for example, neutrons, protons, or negative pi mesons. Relatively few workers have focused their attention toward understanding biological factors which may underlie the successful use of low activity interstitial or intracavitary sources, or the promising results of hyperfractionation; treatment modalities readily available to all radiotherapists and their patients throughout the world. We plan to continue studying dose-rate and dose-fractionation effects on the life cycle and survival of cells with an emphasis on factors which influence the dose-rate effect. Differences in low dose rate responses for log and plateau phase cultures of "transformed" and "non-transformed" cells, hyperthermia effects, and human and rodent cell line comparisons would be studied. Damage end points measured would be cell killing and life cycle perturbations. For the latter, conventional analysis in addition to Flow Microfluorometry (FMF) (sometimes known as Flow Cytometry-FCM) would be used. Experiments are proposed to study complementation of lethal damage in irradiated cells using cell fusion techniques; and methods are described for isolating radiosensitive mutants of CHO cells to study genetic control of radiosensitivity and for possible use in studying radiosensitivity of human plus rodent hybrid cells. We also plan to study early stages of chromosomal aberration formation by the induction of premature chromosome condensation (PCC), and to compare aberration frequency and cell killing when different portions of the cell genome are damaged by BUdr plus light treatment.